Have to second Leigh on Dave Malkoff and Sophia, Decker and Tracy, Eden and Izzy from Suzanne Brockmann's Troublemaker series. Probably Meg and John from the Defiant Hero too. Those couples were giant misses for me.

Bracing myself for flying, rotten tomatoes here, but I submit John and Xhex from the Black Dagger Brotherhood. I loved their book, but in every book since, I've kind of hated them a little, especially since they *SPOILER* split up in the first pages of the book directly after theirs. Really?!

Seconding scarlettleigh's list. I made a weird kind of peace with Dave & Sophia, mostly because I got really tired of her story & stopped caring about how it turned out, but my hatred for the pairings of Decker & Tracy and Izzy & Eden will never end.

@MFrampton
I thank you for not letting me be the only one. I was so excited for Lothaire's book...until I was about 1/3 of the way through it. The book itself was just blah however, combine that with the fact that his Bride was so unworthy and so boring that I too have forgotten her name, and it quickly became one of the worst books in the series for me. She fell too far below par for "The Enemy of Old".

In books... BDB's Quinn and Blay. Loved the chemistry and unrequited love throughout the series. And was completely excited for Lover at Last. Then i read the book. And they ended up whiny and just not at all what I expected.
In TV... Sam and Amelia from Supernatural. Absolutely no chemistry what so ever.

BILL AND SOOKIE. Bill is one of the worst characters ever written, especially in the show. Every time he speaks I want to gag and watching him and sookie together is so blah. It's hard to imagine Anna Paqin and Stephen Moyer being married ew.

I second Bill and Sookie, oliviacarel -- but then, c'mon, **HIGHLIGHT FOR POSSIBLE SPOILER**Sookie and Sam! Not entirely sure which is worse, chemistry-wise. To be honest, I was always pulling for Quinn the Weretiger, but maybe that's just because I love the idea of a weretiger. There should be more books about weretigers! Get to it, PR writers of the world.

@ Micah

John Matthew and Xhex are now officially INSUFFERABLE. Seriously, they make the bleak and blah Phury and Cormia look like... well, like John Matthew and Xhex in every book before Lover Mine. (But hey! A little kindness towards my poor Qhuinn and Blay please, jarielynn. Have they not suffered enough?)

Other couples I never really bought include Anita Blake and Richard (JC all the way, baby!) and -- obviously -- Harry Potter and Ginny Weasley. But even they must bow down to the Winners and Still Champions When it Comes to No Chemistry Whatsoever: Anakin Skywalker and Padme Amidala!

(Hmm, Natalie Portman shows up again. Good thing she's shown some rapport with Zach Braff, Mila Kunis and that guy from Where the Heart Is, or we have to conclude it's just her.)

I didn't like House and Cuddy together. Their sexual tension was better to watch.

Some actors just don't have chemistry. Chris H. and Natalie P. (Thor/Jane) do not have it. Emily R. (Audrey) and Lucas B. (Nathan) from Haven do not have it either. I like the actors & characters, just not in a romantic relationship.

I remember another one that shouldn't have been coupled: Dawson and Joey (Dawson's Creek). Oh, my teen years.... Joey and Pacey had amazing chemistry though.

@stacymd2 -- I gave up on Supernatural very early in the beginning because ZOMG scary!! =O Now I keep reading how good it is and I've been meaning to catch up on it. I just never seem to manage to actually watch it while it's still light out. lol